Cordyceps Cicadae Research Articles

Polysaccharides from Cordyceps cicadae Ameliorate Reproductive Impairments in Male Mouse through the Hypothalamic-Pituitary-Testicular Axis.

Cordyceps cicadae polysaccharides have received attention due to their potential in treating hyperglycemia and enhancing renal function. The beneficial effect of the purified C. cicadae polysaccharides fraction (CCP-1) on the reproductive impairments and spermatogenesis dysfunction of immunocompromised mice is unavailable and is studied herein. The study establishes a GC-1 spg cell apoptosis model induced by TNF-α+SM-164 (TS) and male mouse reproductive injury model induced by cyclophosphamide (CTX), and then intervened by CCP-1. CCP-1 improves the viability of GC-1 spg cell and inhibits cells apoptosis induced by TS in vitro. CCP-1 enhances sperm quality and spermatogenesis function, as well as ameliorating the histological lesions in the hypothalamus, testicular, and kidney. CCP-1 elevates gonadotropin-releasing hormone (GnRH) level that secreted by the hypothalamus, and increases the levels of follicle stimulating hormone (FSH) and luteizing hormone (LH) in the anterior pituitary stimulated by GnRH, and promotes the secretion of testosterone (T) by testis. Moreover, CCP-1 could protect the reproductive system by activating reproductive regulatory pathway such as SCF/C-kit pathway and inhibiting apoptotic signaling pathway such as Bax/Caspase-3 pathway. These results manifest that CCP-1 could serve as a natural promising reproductive system protective supplement for ameliorating CTX biotoxicity.

Pharmacological and economical aspects of important species of Cordyceps sensu lato: A review.

Cordycepsis a well-known endo-parasitic fungus commonly used in traditional Chinese medicine for a long time. The demand for Cordyceps is increasing daily because it is commonly used as a nutritional food, medicine, and supplement owing to its natural source. It is very attractive in almost all countries with no side effects. Most Cordyceps species have been studied in China, Bhutan, India, Japan, South Korea, and Nepal. We have discussed the important contents of Cordyceps, dietary source and nutritional value of Cordyceps, multiple pharmacological properties of four important Cordyceps species, Ophiocordyceps sinensis, Cordyceps militaris, Cordyceps cicadae, and Cordyceps tenuipes, along with the economic status of Cordyceps and its benefits in terms of medicine, supplements, and the cosmetics industry. Owing to the high demand and several benefits of Cordyceps, it offers mysterious economic improvements in developed and underdeveloped countries. Therefore, more attention is required to save the endangered species of Cordyceps to fulfil the medicinal and nutritional demands worldwide.

A rho-type GTPase activating protein affects the growth and development of Cordyceps cicadae.

Cordyceps cicadae is recognized for its medicinal properties, attributed to bioactive constituents like polysaccharides and adenosine, which have been shown to improve kidney and liver functions and possess anti-tumor properties. Rho GTPase activating proteins (Rho GAPs) serve as inhibitory regulators of Rho GTPases in eukaryotic cells by accelerating the GTP hydrolysis of Rho GTPases, leading to their inactivation. In this study, we explored the function of the CcRga8 gene in C. cicadae, which encodes a Rho-type GTPase activating protein. Our study found that the knockout of CcRga8 resulted in a decrease in polysaccharide levels and an increase in adenosine concentration. Furthermore, the mutants exhibited altered spore yield and morphology, fruiting body development, decreased infectivity, reduced resistance to hyperosmotic stress, oxidative conditions, and cell wall inhibitors. These findings suggest that CcRga8 plays a crucial role in the development, stress response, and bioactive compound production of C. cicadae.

Exploiting the roles of nitrogen sources for HEA increment in Cordyceps cicadae.

Cordyceps cicadae, as a new food ingredient, is a valuable edible and medicinal fungi. However, its resources are severely depleted due to environmental limitations and excessive harvesting practices. N6-(2-hydroxyethyl) adenosine (HEA), as an important product of Cordyceps cicadae, has the potential to be used in medical industry due to its diverse disease curing potential. However, the disclosure of HEA synthesis still severely limited its application until now. In this study, the kinetic curves for adenosine and HEA under shaker fermentation were explored. The kinetics of HEA and adenosine production exhibited a competitive pattern, implicating a possibility of sharing a same step during their synthesis. Due to HEA as a derivative of nitrogen metabolism, the effect of different nitrogen sources (peptone, yeast extract, ammonium sulfate, diammonium oxalate monohydrate, ammonium citrate dibasic, and ammonium citrate tribasic) on HEA production in Cordyceps cicadae strain AH 10-4 had been explored under different incubation conditions (shaker fermentation, stationary fermentation, and submerged fermentation). Our results indicated that the complex organic nitrogen sources were found to improve the accumulation of HEA content under shaker fermentation. In contrast, the optimal nitrogen source for the accumulation of HEA under stationary fermentation and submerged fermentation was ammonium citrate tribasic. But submerged fermentation obviously shortened the incubation time and had a comparable capacity of HEA accumulation by 2.578 mg/g compared with stationary fermentation of 2.535 mg/g, implicating a possibility of scaled-up production of HEA in industry by submerged fermentation. Based on the dramatic HEA production by ammonium sulfate as nitrogen resources between stationary and shaker fermentations, alanine, aspartate and glutamate as well as arginine metabolic pathway were related to the production of HEA by comparative transcriptome. Further investigation indicated that glutamic acid, which is an analog of Asp, showed an optimum production of HEA in comparison with other amino acids.

The composition and function of bacterial communities in Bombyx mori (Lepidoptera: Bombycidae) changed dramatically with infected fungi: A new potential to culture Cordyceps cicadae.

Cordyceps cicadae (Hypocreales: Cordycipitaceae) is a renowned entomopathogenic fungus used as herbal medicine in China. However, wild C. cicadae resources have been threatened by heavy harvesting. We hypothesised that Bombyx mori L. (Lepidoptera: Bombycidae) could be a new alternative to cultivate C. cicadae due to the low cost of rearing. Bacterial communities are crucial for the formation of Cordyceps and for promoting the production of metabolites. To better understand the bacterial community structure associated with Cordyceps, three Claviciptaceae fungi were used to explore the pathogenicity of the silkworms. Here, fifth-instar silkworms were infected with C. cicadae, Cordyceps cateniannulata (Hypocreales: Cordycipitaceae) and Beauveria bassiana (Hypocreales: Cordycipitaceae). Subsequently, we applied high-throughput sequencing to explore the composition of bacterial communities in silkworms. Our results showed that all three fungi were highly pathogenic to silkworms, which suggests that silkworms have the potential to cultivate Cordyceps. After fungal infection, the diversity of bacterial communities in silkworms decreased significantly, and the abundance of Staphylococcus increased in mummified larvae, which may play a role in the death process when the host suffers infection by entomopathogenic fungi. Furthermore, there were high similarities in the bacterial community composition and function in the C. cicadae and C. cateniannulata infected samples, and the phylogenetic analysis suggested that these similarities may be related to the fungal phylogenetic relationship. Our findings reveal that infection with different entomopathogenic fungi affects the composition and function of bacterial communities in silkworms and that the bacterial species associated with Cordyceps are primarily host dependent, while fungal infection affects bacterial abundance.

Roles of CcDFR and CcOMT9 in the cyanidin biosynthesis and development of Cordyceps cicadae.

Cordyceps cicadae is a traditional Chinese medicinal fungus known for its rich production of bioactive substances, particularly cyanidin, an anthocyanin commonly found in plants with notable anti-inflammatory, anti-tumor, antiviral, and antibacterial properties. This study revealed two key genes, CcDFR and CcOMT9, affecting cyanidin biosynthesis in C. cicadae. The roles of these genes in cyanidin production, growth, and development were elucidated through the gene knockout method, phenotypic analysis, transcriptomics, and metabolomics. CcDFR deletion led to reduced cyanidin-3-O-glucoside (C3G), suppressed expression of cyanidin biosynthesis genes, impaired synnemata formation, decreased polysaccharide and adenosine content, and diminished chitinase activity. Meanwhile, the ΔCcOMT9 mutant exhibited an increase in C3G production, promoted expression of cyanidin biosynthesis genes and rising bioactive compounds, suppressed RNA methylation, and led to phenylalanine accumulation with no effect on fruiting body formation. We revealed a distinct anthocyanin biosynthesis pathway in C. cicadae and identified two genes with opposite functions, laying the foundation for future genetic modification of cyanidin-producing strains using modern biological techniques. This will shorten the production period of this valuable compound, facilitating the industrial-scale production of cyanidin.

A New Macrolide from the Strain Cordyceps spp. from Cell Fusion between Cordyceps militaris and Cordyceps cicadae

A New Macrolide from the Strain Cordyceps spp. from Cell Fusion between Cordyceps militaris and Cordyceps cicadae

Soluble dietary fibers from solid-state fermentation of wheat bran by the fungus Cordyceps cicadae and their effects on colitis mice.

Ulcerative colitis is a chronic inflammatory disease with a complex pathogenesis for which there is no definitive therapeutic agent. Fermentation, as a green and efficient bioprocessing technique, has been shown to enhance the biological activity of food ingredients. Soluble dietary fiber isolated from plants is thought to have the potential to prevent and alleviate ulcerative colitis. This work was designed to study the differences in the chemical properties of the soluble dietary fiber from wheat bran fermented by Isaria cicadae Miq. (FSDF) and the unfermented soluble dietary fiber from wheat bran (UFSDF) and their effects on colitis mice. The results showed that FSDF and UFSDF differed in molecular weight, monosaccharide compositions, and surface morphology. In addition, supplementation with UFSDF and FSDF ameliorated the symptoms of DSS-induced colitis in mice by attenuating body weight loss, decreasing the disease activity index and splenic index, shortening the length of the colon, and attenuating colonic tissue damage. UFSDF and FSDF also increased the production of the anti-inflammatory cytokine IL-10 and inhibited the expression of IL-6, IL-1β, and TNF-α. The results of gut flora and short-chain fatty acid analyses showed that UFSDF and FSDF improved the diversity of gut microbiota, up-regulated the abundance of some beneficial bacteria such as Akkermansia and Muribaculaceae, increased the levels of acetic acid, propionic acid, and butyric acid, and restored dextran sodium sulfate (DSS)-induced dysbiosis of the intestinal flora in mice. These findings provide guidance for the development of FSDF and UFSDF as functional foods for the relief of ulcerative colitis.

Characterization of Metabolite Landscape Distinguishes Medicinal Fungus Cordyceps sinensis and other Cordyceps by UHPLC-Q Exactive HF-X Untargeted Metabolomics

Cordyceps represent a valuable class of medicinal fungi with potential utilization. The overexploitation and resource scarcity of Cordyceps sinensis (CS) have led to the emergence of Cordyceps such as Cordyceps militaris (CM) and Cordyceps cicadae (CC) as substitutes. The medicinal value of CS is often considered superior to other Cordyceps, potentially owing to differences in active ingredients. This study aimed to evaluate the differences in the composition and abundance of the primary and secondary metabolites of CS and its substitutes by untargeted metabolomics. A total of 4671 metabolites from 18 superclasses were detected. CS and its substitutes were rich in amino acids, lipids, organic acids, and their derivatives. We statistically analyzed the metabolites and found a total of 285 differential metabolites (3′-Adenylic acid, O-Adipoylcarnitine, L-Dopachrome, etc.) between CS and CC, CS and CM, and CM and CC, which are potential biomarkers. L-glutamate and glycerophospholipids were differential metabolites. A KEGG enrichment analysis indicated that the tyrosine metabolic pathway and tryptophan metabolism pathway are the most differentially expressed pathways among the three Cordyceps. In contrast, CS was enriched in a higher abundance of most lipid metabolites when compared to CM and CC, which may be an indispensable foundation for the pharmacological functions of CS. In conclusion, systematic, untargeted metabolomics analyses for CS and other Cordyceps have delivered a precious resource for insights into metabolite landscapes and predicted potential components of disease therapeutics.

Edible and Medicinal Progress of Cryptotympana atrata (Fabricius) in China.

As an important resource insect, the Cryptotympana atrata is widely distributed in the eastern and central parts of China. The cicada slough is one of the traditional crude drugs in East Asia, and the main component is polysaccharide, which has the functions of anti-convulsion, relieving asthma and improving lipid metabolism. The parasitoid fungus Cordyceps cicadae, which grows inside the cicada nymphs and forms the fruiting bodies on the surface of the host's carcass, is also known as the "cicada flower" in China. The Cordyceps cicadae is another old, traditional Chinese medicine, which has been used as a tonic and medicine to nourish and regulate human immunity for centuries. For the further development and utilization of the golden cicada, this paper summarized the C. atrata from the aspects of their biological characteristics, distribution area, life cycle, history of edible and medicinal use, edible methods and nutritional compositions; emphatically introduced the edible and potential medicinal value of the C. atrata; and specifically expounded the research progress of its application. As one popular insect food, the prospects for the development of C. atrata have also been put forward, especially in artificial breeding technology, food safety risk assessment and medicinal value utilization.

Immunomodulation of RAW264.7 cells by CP80-1, a polysaccharide of Cordyceps cicadae, via Dectin-1/Syk/NF-κB signaling pathway

ABSTRACT Cordyceps cicadae is a rare edible and medicinal entomogenous fungus. Here, the structural characteristics and immunomodulatory activity of C. cicadae polysaccharide CP80-1 were preliminarily elucidated. It showed that CP80-1 of 250.431 kDa was mainly composed of glucose, xylose and rhamnose. Physiologically, CP80-1 can regulate the immune of RAW264.7 cells by promoting the proliferation, phagocytosis, and secretion of nitric oxide (NO), tumor necrosis factor (TNF)-α, interleukin (IL)−1β, and interleukin (IL)−6. However, these effects were significantly attenuated when Dectin-1 receptor expression was inhibited by laminarin. Moreover, laminarin down-regulated the mRNA levels of relevant genes, inhibited CP80-1-driven expression of proteins related to spleen tyrosine kinase (Syk) and nuclear factor kappa-B (NF-κB) signaling pathway. Additionally, CP80-1 induced the nuclear translocation of NF-κB subunit p65 in RAW264.7 cells. These results suggest that CP80-1 may activate RAW264.7 cells by regulating the Dectin-1/Syk/NF-κB signaling pathway, which provides theoretical basis for the development of C. cicadae in immunomodulation.

Cordyceps cicadae polysaccharides alleviate hyperglycemia by regulating gut microbiota and its mmetabolites in high-fat diet/streptozocin-induced diabetic mice.

The polysaccharides found in Cordyceps cicadae (C. cicadae) have received increasing academic attention owing to their wide variety of therapeutic activities. This study evaluated the hypoglycemic, antioxidant, and anti-inflammatory effects of polysaccharides from C. cicadae (CH-P). In addition, 16s rDNA sequencing and untargeted metabolomics analysis by liquid chromatography-mass spectrometry (LC-MS) were used to estimate the changes and regulatory relationships between gut microbiota and its metabolites. The fecal microbiota transplantation (FMT) was used to verify the therapeutic effects of microbial remodeling. The results showed that CH-P treatment displayed hypoglycemic, antioxidant, and anti-inflammatory effects and alleviated tissue damage induced by diabetes. The CH-P treatment significantly reduced the Firmicutes/Bacteroidetes ratio and increased the abundance of Bacteroides, Odoribacter, Alloprevotella, Parabacteroides, Mucispirillum, and significantly decreased the abundance of Helicobacter and Lactobacillus compared to the diabetic group. The alterations in the metabolic pathways were mostly related to amino acid biosynthesis and metabolic pathways (particularly those involving tryptophan) according to the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Correlation analysis showed that Bacteroides, Odoribacter, Alloprevotella, Parabacteroides, and Mucispirillum were positively correlated with indole and its derivatives, such as 5-hydroxyindole-3-acetic acid. Indole intervention significantly improved hyperglycemic symptoms and insulin sensitivity, and increased the secretion of glucagon-like peptide-1 (GLP-1) in diabetic mice. FMT reduced blood glucose levels, improved glucose tolerance, and increased insulin sensitivity in diabetic mice. However, FMT did not significantly improve GLP-1 levels. This indicates that C. cicadae polysaccharides alleviate hyperglycemia by regulating the production of metabolites other than indole and its derivatives by gut microbiota. This study provides an important reference for the development of novel natural products.

Preventative Effects of Cordyceps cicadae Mycelial Extracts on the Early-Stage Development of Cataracts in UVB-Induced Mice Cataract Model.

Cataracts, a prevalent age-related eye condition, pose a significant global health concern, with rising rates due to an aging population and increased digital device usage. In Taiwan, cataract prevalence is particularly high, reaching up to 90% among individuals aged 70 and above. The lens of the eye absorbs short-wave light, which can lead to oxidative stress in lens epithelial cells and contribute to cataract formation. Exposure to ultraviolet (UV) light further exacerbates the risk of cataracts by generating reactive oxygen species. Heat-shock proteins (HSPs), involved in protein maintenance and repair, have been linked to cataract development. Cordyceps cicadae (C. cicadae), a traditional Chinese medicine, has a long history of use and is known for its pharmacological effects. N6-(2-hydroxyethyl) adenosine (HEA), a bioactive compound found in C. cicadae, exhibits anti-inflammatory, immunomodulatory, and neuroprotective properties. Previous studies have shown that C. cicadae mycelial extracts improve dry eye disease and reduce intraocular pressure in animal models. Additionally, C. cicadae possesses antioxidant properties, which are beneficial for combating cataract formation. In this study, we aim to evaluate the preventive efficacy of C. cicadae mycelial extracts in UV-induced cataract development. By investigating the ameliorative effects of C. cicadae on eye diseases and its potential role in ocular health improvement, we hope to uncover new options for cataract prevention and provide insights into the mechanisms of action. The findings of this research could provide a novel approach for nutritional supplements targeting cataract prevention, offering potential benefits in the field of ocular health.

Aqueous extract of Cordyceps cicadae (Miq.) promotes hyaluronan synthesis in human skin fibroblasts: A potential moisturizing and anti-aging ingredient.

Cordyceps cicadae (Miq.) is an edible fungus with unique and valuable medicinal properties that is commonly used in traditional Chinese medicine, but its anti-aging effects on the skin fibroblast are not well studied. The aim of the present study was to analyze the active components of aqueous C. cicadae extract (CCE), determine the effects of CCE on hyaluronan synthesis in human skin fibroblasts, and explore the underlying mechanisms. The results of this study indicate that CCE was rich in polysaccharides, five alditols (mainly mannitol), eight nucleosides, protein, and polyphenols, which were present at concentrations of 62.7, 110, 8.26, 35.7, and 3.8 mg/g, respectively. The concentration of extract required to inhibit 50% of 2,2-azino-bis (3-ethylbenzothiazo-line-6-sulphonic acid) (ABTS) and 2,2-diphenyl-1-picrylhydrazil (DPPH) radical scavenging capacities were 0.36 ± 0.03 and 4.54 ± 0.10 mg/mL, respectively, indicating that CCE exhibits excellent antioxidant activities. CCE showed no cytotoxicity to skin fibroblasts at concentrations ≤ 100 μg/mL, and promoted HA synthesis in fibroblasts. Treatment of fibroblast cells with 100 μg/mL CCE enhances the HA content to 1293 ± 142 ng/mL, which is significantly more than that in the non-treatment (NT) group (p = 0.0067). Further, RNA sequencing detected 1,192 differentially expressed genes (DEGs) in CCE-treated fibroblasts, among which 417 were upregulated and 775 were downregulated. Kyoto Encyclopedia of Genes (KEGG) and Genomes pathway (GO) analysis based on RNA sequencing revealed that CCE mainly affected cytokine-cytokine receptor interaction regulated by HA synthesis-related genes. CCE upregulated HA synthase 2 (HAS2), epidermal growth factor (EGF)-related genes, heparin-binding EGF-like growth factor, C-C motif chemokine ligand 2, interleukin 1 receptor-associated kinase 2, and other genes related to fibroblast differentiation and proliferation. CCE downregulated the gene of matrix metallopeptidase 12 (MMP12), which leads to cell matrix loss. RT-qPCR further verified CCE significantly upregulated HAS2 expression and significantly downregulated MMP12 expression, thus promoting hyaluronan synthesis. CCE shows potential as a moisturizer and anti-aging agent in functional foods and cosmetics.

A New Galactoglucomannan from the Mycelium of the Medicinal Parasitic Fungus Cordyceps cicadae and Its Immunomodulatory Activity In Vitro and In Vivo.

A new galactoglucomannan (C-0-1) was purified from the medicinal parasitic fungus of Cordyceps cicadae using an anion-exchange column and gel permeation column. The results of high-performance liquid chromatography and high-performance gel permeation chromatography indicated that C-0-1 consists of galactose, glucose, and mannose in a ratio of 5:1:4 and has a molecular weight of 23.3 kDa. The combined structural elucidation analysis methods including partial acid hydrolysis, methylation analysis, and NMR experiments revealed that C-0-1 was a comb-like polysaccharide with a core structure including (1→2)-α-D-Manp residues in the backbone and branches at O-6 of the main chain. (1→4)-α-D-Glcp, (1→2)-β-D-Galf, (1→2,6)-β-D-Galf, and terminal β-Galf were located at the side chains. An in vitro experiment using RAW 264.7 cells indicated that C-0-1 exhibits good immunomodulatory activity by enhancing inducible nitric oxide synthase secretion and the production of some major inflammatory cytokines. On inhibiting the cytokine production using anti-pattern recognition receptors antibodies, it was revealed that the activation of macrophages is mainly carried out by C-0-1 through the mannose receptor. Toll-like receptor 4 and Toll-like receptor 2 were also involved in this identification process. An in vivo experiment on immunosuppressive mice treated with cyclophosphamide indicated that C-0-1 improves the secretion of serum-related cytokines (IFN-γ, TNF-α, IL-2, IL-4, and IL-10) and affects the balance of T helper cells Th1/Th2. Given the structural and bioactivity similarity between Cordyceps cicadae and Cordyceps sinensis, we can conclude that Cordyceps cicadae could be used as an important medicinal fungus like Cordyceps sinensis.

Cordyceps cicadae NTTU 868 Mycelia Fermented with Deep Ocean Water Minerals Prevents D-Galactose-Induced Memory Deficits by Inhibiting Oxidative Inflammatory Factors and Aging-Related Risk Factors.

Cordyceps cicadae, a medicinal fungus that is abundant in bioactive compounds such as N6-(2-hydroxyethyl)-adenosine (HEA) and polysaccharides, possesses remarkable anti-inflammatory, antioxidant, and nerve damage recovery properties. Deep ocean water (DOW) contains minerals that can be absorbed and transformed into organic forms by fungi fermentation. Recent studies have shown that culturing C. cicadae in DOW can enhance its therapeutic benefits by increasing the levels of bioactive compounds and minerals' bioavailibility. In this study, we investigated the effects of DOW-cultured C. cicadae (DCC) on brain damage and memory impairment induced by D-galactose in rats. Our results indicate that DCC and its metabolite HEA can improve memory ability and exhibit potent antioxidant activity and free radical scavenging in D-galactose-induced aging rats (p < 0.05). Additionally, DCC can mitigate the expression of inflammatory factors, such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS), thereby preventing brain aging. Furthermore, DCC showed a significant decrease in the expression of the aging-related proteins glial fibrillary acidic protein (GFAP) and presenilin 1 (PS1). By reducing brain oxidation and aging-related factors, DOW-cultured C. cicadae demonstrate enhanced anti-inflammatory, antioxidant, and neuroprotective effects, making it a promising therapeutic agent for preventing and treating age-related brain damage and cognitive impairment.

Structural Characterization and Hypoglycemic Function of Polysaccharides from Cordyceps cicadae.

The polysaccharides isolated and purified from different parts of the medicinal fungus Cordyceps cicadae were identified, and three extracts displaying significant biological activities were selected for further study. The bacterium substance polysaccharides (BSP), spore powder polysaccharides (SPP), and pure powder polysaccharides (PPP) were separated, purified, and collected from the sclerotia, spores, and fruiting bodies of Cordyceps cicadae, respectively. The structures of Cordyceps cicadae polysaccharides were analyzed using gas chromatography, Fourier-transform infrared spectroscopy, methylation analysis, and one-dimensional (1H and 13C) nuclear magnetic resonance spectroscopy. Moreover, the hypoglycemic effect of Cordyceps cicadae polysaccharides was examined in both in vitro and in vivo models. BSP, SPP, and PPP significantly increased glucose absorption in HepG2 cells, and alleviated insulin resistance (IR) in the in vitro model. SPP was the most effective, and was therefore selected for further study of its hypoglycemic effect in vivo. SPP effectively improved body weight and glucose and lipid metabolism in type 2 diabetes model mice, in addition to exerting a protective effect on liver injury. SPP regulated the mRNA expression of key PI3K/Akt genes involved in the insulin signaling pathway. The hypoglycemic mechanism of SPP may reduce hepatic insulin resistance by activating the PI3K/Akt signaling pathway. Spore powder polysaccharides (SPP) extracted from Cordyceps cicadae effectively improved body weight and glucose and lipid metabolism in type 2 diabetes model mice, in addition to exerting a protective effect on liver injury. The mechanism underlying the hypoglycemic effect of SPP regulates the mRNA expression of key PI3K/Akt genes involved in the insulin signaling pathway to alleviate insulin resistance. Our results provide a theoretical basis for research into the hypoglycemic effect of Cordyceps cicadae, and lay the foundation for the development of functional products.

Amelioration of Cyclosporine A-Induced Acute Nephrotoxicity by Cordyceps cicadae Mycelia via Mg+2 Reabsorption and the Inhibition of GRP78-IRE1-CHOP Pathway: In Vivo and In Vitro.

Fruiting bodies of Cordyceps cicadae (CC) have been reported to have a therapeutic effect in chronic kidney disease. Due to the rare and expensive resources from natural habitats, artificially cultivated mycelia using submerged liquid cultivation of CC (CCM) have been recently developed as an alternative to scarce sources of CC. However, little is known regarding potential protective effects of CCM against cyclosporine A (CsA)-induced acute nephrotoxicity in vivo and in vitro. In this study, male Sprague-Dawley rats were divided into six groups: control, CCM (40 mg and 400 mg/kg, orally), CsA (10 mg/kg, oral gavage), and CsA + CCM (40 mg and 400 mg/kg, orally). At the end of the study on day 8, all rats were sacrificed, and the blood and kidneys retrieved. CsA-induced acute nephrotoxicity was evident by increased levels of blood urea nitrogen (BUN). Levels of the endoplasmic reticulum (ER) resident chaperone glucose regulated protein 78 (GRP 78) were increased significantly in rats with acute nephrotoxicity. BUN and GRP 78 were significantly ameliorated in synchronous oral groups of CCM (40 or 400 mg/kg) plus CsA. Examination of hematoxylin and eosin stained kidney tissues revealed that the combined treatment of CCM slightly improved vacuolization in renal tubules upon CsA-induced damage. CsA-induced down-regulation of protein expression of magnesium ion channel proteins and transient receptor potential melastatin 6 and 7 were abolished by the combined treatment of CCM. CCM has the potential to protect the kidney against CsA-induced nephrotoxicity by reducing magnesium ion wasting, tubular cell damage, and ER stress demonstrated further by human renal proximal tubular epithelial cell line HK-2. Our results contribute to the in-depth understanding of the role of polysaccharides and nucleobases as the main secondary metabolites of CCM in the defense system of renal functions in CsA-induced acute nephrotoxicity.

Synergistic effects of the Se and Zn supplemental combination on the nutrient improvement of mannitol and adenosine and the multi-element bioaccessibility in Cordyceps cicadae

Cordyceps cicadae is an edible mushroom. Selenium (Se) and zinc (Zn) are essential microelements for humans. To develop Se–Zn biofortification strategies for C. cicadae, the effects of three Se species (selenium nanoparticles, selenite, and selenate) and two Zn species (zinc sulfate and EDTA-zinc) on biomass, mineral elements, mannitol, adenosine, cordycepin, and bioaccessibility were investigated. The fruiting bodies had significant bioaccumulation and biotransformation ability for selenite, which converted selenium nanoparticles, selenite, and selenate into selenocysteine (63.5–70.2%) and selenomethionine (20.4–27.7%). Selenite and selenate eliminated inhibition of fruiting bodies growth by zinc. The synthesis of mannitol and adenosine was promoted by Se–Zn biofortification, while interfering with multi-elements enrichment. During gastrointestinal digestion, over 57.1% of total Se, 41.3% of essential microelements, 100% of selenomethionine, and 6.0% of selenocysteine were released. The release of adenosine and cordycepin in selenite plus zinc sulfate treatment were increased by 21.9% and 106.0% compared with control. The findings indicate that Se–Zn-enriched C. cicadae is a novel Se and Zn supplement.

Cordyceps cicadae and Cordyceps gunnii have closer species correlation with Cordyceps sinensis: from the perspective of metabonomic and MaxEnt models

Cordyceps sinensis is a second-class nationally-protected medicinal fungus and functional food. Cordyceps sinensis resources are endangered, and finding new medicinal materials is a fast and economical way to meet the current demonstrated demand, which can effectively solve the shortage of C. sinensis resources. In this study, the metabolite characteristics of Cordyceps were comprehensively revealed by LC-QTOF-MS technology. The maxent model can be used to predict the habitat suitability distribution of Cordyceps and screen out the main climatic factors affecting its distribution. The correlation model between climate factors and chemical components was established by Pearson correlation analysis. Finally, based on the analysis of climate factors and metabolites, we will analyze the high correlation species with C. sinensis, and develop them as possible alternative species of C. sinensis in the future. The results showed that the suitable area of Cordyceps cicadae demonstrated a downward trend, while that of C. sinensis, Cordyceps militaris and Cordyceps gunnii demonstrated an upwards trend. The suitable areas all shifted to the northwest. The temperature seasonality and max temperature of the warmest month are the maximum climatic factors affecting nucleosides. Compared with C. sinensis, the metabolic spectrum similarities of C. cicadae, C. militaris, and C. gunnii were 94.42%, 80.82%, and 91.00%, respectively. Cordyceps sinensis, C. cicadae, and C. gunnii were correlated well for compounds and climate factors. This study will explore whether C. cicadae, C. militaris and C. gunnii can be used as substitutes for C. sinensis. Our results may provide a reference for resource conservation and sustainable utilization of endangered C. sinensis.